Juvenile Idiopathic Arthritis M08.-

The term "juvenile idiopathic arthritis" (JIA) is used to describe a heterogeneous group of chronic rheumatic joint diseases in childhood. By definition, juvenile idiopathic arthritis occurs before the age of 16 and persists for longer than 6 weeks.

Systemic juvenile idiopathic arthritis: the term "systemic JIA" is synonymous with Still's syndrome (ICD-10: M08.2).

Oligoarticular juvenile idiopathic arthritis: JIA is called oligoarticular when only one to four joints are affected (ICD-10: M08.4).

Polyarticular juvenile idiopathic arthritis: JIA is called polyarticular when five or more joints are affected.

• Polyarticular juvenile idiopathic arthritis, rheumatoid factor positive (ICD-10: M08.0).
• Polyarticular juvenile idiopathic arthritis, rheumatoid factor negative (ICD-10: M08.3)

Enthesis-associated juvenile idiopathic arthritis: Enthesis-associated arthritis involves the tendon attachments (entheses) (ICD-10: M08.8).

Juvenile psoriatic arthritis: In juvenile psoriatic arthritis, additional psoriatic involvement of the skin and nails is to be expected (ICD-10: L40.5).

Undifferentiated arthritis: Rheumatoid forms that cannot be assigned to a specific subtype are grouped under the term "undifferentiated arthritis".

Incidence: 4-5 / 100,000 children. The prevalence is 20-30 cases per 100,000 children and adolescents.

The cause of juvenile idiopathic arthritis is not yet clear. It is assumed that autoimmune mechanisms may promote the onset of the disease in the presence of genetic predisposition. Numerous gene loci are involved in the predisposition to the disease (polygenic disease), different genes predominate for different subtypes, and significantly different gene loci are often involved than in adult-onset rheumatoid diseases. One susceptibility gene is the CD25 gene (IL2RA gene), which encodes the IL-2 receptor alpha. However, latent infections (e.g. with parvovirus B19 or rubella virus) and trauma probably also play an initiating role.

Age of manifestation <16 years

General symptoms: Initial symptoms (also during the course of the disease) are often fatigue, tearfulness and poor performance. The leading symptoms of arthritis joint inflammation (pain, swelling, hyperthermia and restriction of movement) do not always occur in children, in contrast to adults. Thus, younger children often do not express the pain directly. They change their behavior, allow themselves to be carried, are whiny during motor activities, and seem to regress. The affected joints are held in a protective posture, usually in flexion. If left untreated, this inactivity in an axial malposition can lead to permanent contractures (shortening of tendons with permanent movement restrictions) and muscle atrophy. Furthermore, asymmetric growth of the joints and adjacent bones may occur. In principle, any joint can be affected. A pressure pain can often be felt over affected joints. The pain is usually reported by the children as moderate and tolerable. Joint pain is typically worse in the morning and after prolonged inactivity ("morning stiffness") and is aggravated by movement of the inflamed joint. Typically, oligoarticular forms begin asymmetrically, preferentially at the large joints of the legs . Polyarticular forms occur symmetrically at the small joints of the hands and feet. Systemic courses and high disease activity may result in slowed growth and development, delayed puberty, and weight loss. Specifically:

• Systemic juvenile idiopathic arthritis: On average, this form of rheumatism first breaks out in eight-year-olds. About 6 out of 100 children with juvenile idiopathic arthritis (JIA) develop systemic juvenile idiopathic arthritis (SJIA). Fever usually occurs in the evening hours. It may be accompanied by a rash. During the first week, joint inflammation may be absent. Then, the large joints are more often affected.
• Oligoarticular juvenile idiopathic arthritis: Oligoarticular JIA is the most common subtype of JIA, accounting for nearly 50% of all cases. JIA is called oligoarticular when only one to four joints are affected. The knee and ankle joints are often affected. This form of rheumatism is or was also called early childhood oligoarthritis, "little girl form" (oligoarthritis type I). Onset: in infancy (between 2 and 6 years). Girls are more often affected. Children with early childhood oligoarthritis have a high risk of developing rheumatoid eye inflammation, chronic iridocyclitis. Regular ophthalmologic check-ups are therefore advisable (initially every 6 to 12 weeks). A characteristic of the disease is the asymmetric involvement of large joints (such as knees and ankles). Occasionally, only one joint is affected (monoarticular form). In some patients, the number of affected joints increases to more than 5 joints after the first 6 months; this manifestation is called extended oligoarthritis. When fewer than 5 joints are affected throughout the course of the disease, it is referred to as persistent oligoarthritis.
• Polyarticular juvenile idiopathic arthritis, rheumatoid factor positive: Five or more joints are already inflamed at onset. Rheumatoid factor positive. This form of rheumatism usually first appears in adolescence. As with seronegative PA, predominantly girls are affected. About 1-2% of all JIA patients (JIA: juvenile idiopathic arthritis) develop seropositive PA.
• Polyarticular juvenile idiopathic arthritis, rheumatoid factor negative: At the beginning of this form of rheumatism, five or more joints become inflamed - often the small finger joints. The rheumatism first breaks out in children of preschool age, especially in girls. Seronegative polyarthritis affects about one in 10 children with juvenile idiopathic arthritis (JIA).
• Enthesis-associated juvenile idiopathic arthritis (EAA): Enthesitis-associated arthritis involves the tendon attachments (entheses). HLA-B27 can usually test positive. Enthesitis means that in this form of rheumatism, the tendon attachments are affected by inflammation in addition to the joints. Tendon sheaths can also be affected (tenosynovitis). In the beginning, usually only a few large joints of the legs and feet, such as the knee and ankle joints and the metatarsophalangeal joint of the big toe, show inflammatory processes. The onset of the disease is usually at school age (predominantly boys at puberty). About 10% of children with JIA (juvenile idiopathic arthritis) are affected by EAA.
• Juvenile psoriatic arthritis: Psoriatic arthritis describes joint inflammation that occurs in association with psoriasis. Often psoriatic nail changes, swollen fingers or toes are observed years before the onset of the classic cutaneous manifestation of psoriasis. Arthritides may be present in a few or many joints. On average, the first signs appear at age 5 years. About 8 out of 100 children with JIA (Juvenile Idiopathic Arthritis) are patients with Juvenile Psoriatic Arthritis.

MRI, laboratory, if necessary joint puncture or synovial biopsy

There is no indicative laboratory value with which a JIA can be clearly diagnosed. It is useful to determine the following laboratory values:

• Rheumatoid factor
• ANA (often detectable in patients with oligoarticular JIA with early onset). These JIA patients are at high risk for chronic iridocyclitis!
• HLA-B27 (in up to 80% of patients with enthesitis-associated arthritis); in contrast, it is detectable in only 5-8% of healthy individuals.
• ESR; C-reactive protein (CRP)

Other immunological or rheumatic diseases. These include reactive arthritides in chronic intestinal inflammations, such as Crohn's disease and ulcerative colitis. Furthermore in the context of autoimmune diseases such as systemic lupus erythematosus, dermatomyositis systemic scleroderma.

The primary goal of drug therapy is the permanent regression (remission) of disease activity by suppressing the inflammatory mechanisms. This protects the affected children and adolescents from permanent joint and organ damage.

Non-steroidal anti-inflammatory drugs (NSAIDs), cortisone preparations, basic drugs and biologics are used. The dose depends on the body weight.

Furthermore, rehabilitative measures (exercise therapies) and sports activities are of great importance.

In approximately 50% of patients with systemic juvenile idiopathic arthritis, the disease is no longer active in adulthood.

RF-positive polyarticular JIA more often shows a progressive course and can lead to severe joint damage. This pediatric form is the adult-onset counterpart of rheumatoid factor-positive (RF) rheumatoid arthritis.

RF-negative polyarticular JIA is considered to have a better prognosis than RF-positive polyarticular JIA. Joint damage occurs in only about 25% of patients.

In oligoarticular JIA, the prognosis for the joints is often good if the disease remains confined to a few joints (so-called persistent oligoarthritis). Patients in whom joint involvement extends to more than 4 joints (extended oligoarthritis) have the same prognosis as patients with polyarticular RF-negative JIA.

1. Chua-Aguilera CJ et al (2017) Skin manifestations of rheumatoid arthritis, juvenile idiopathic arthritis, and spondyloarthritides. Clin Rev Allergy Immunol 53:371-393.
2. Ergun T et al. (2008) Skin manifestations of rheumatoid arthritis: a study of 215 Turkish patients. Int J Dermatol 47:894-902.
3. Eveillard LA et al.(2022) Association of atypical skin manifestations at the onset of systemic juvenile idiopathic arthritis with difficult-to-treat disease: A retrospective multicenter study. J Am Acad Dermatol S0190-9622(22)02439-2.
4. Magro CM et al (2003) The spectrum of cutaneous lesions in rheumatoid arthritis: a clinical and pathological study of 43 patients. J Cutan Pathol 30:1-10.
5. Sayah A et al (2005) Rheumatoid arthritis: a review of the cutaneous manifestations. J Am Acad Dermatol 53:191-209; quiz 210-2.